The appearance of medical adhesive changes the concept of traditional medicine relying only on stitching wounds. The use of adhesion to replace or assist stitching not only has the advantages including simple operation and no secondary damage to wounds, but also can advantageously apply to or assist the application to soft tissues that are relatively difficult to stitch, for example, liver and pancreas, organs, bones and other parts. In addition, for large superficial hemorrhage, abrasions, burns, battlefield injuries, field damage, intestinal leakage and the like, such medical adhesive can also form a protective film over wounds by means of coverage hemostasis, so as to achieve the purpose of hemostasis and prevention from external infection.
Alkyl α-cyanoacrylate is the most widely used type of medical adhesive. In its structure, αcarbon atom is linked to a cyano group and an ester group, so the double bond has a very low electron cloud density, and it has a very strong electron-withdrawing property, and can generate instantaneous intermolecular polymerization under the action of infinitesimal anions (amino group, hydroxyl group, trace weak basic material such as steam and the like on the surface of biological tissues). In general, alkyl α-cyanoacrylate as monomer is in liquid state, and, after being used by spraying or smearing to contact with human tissue, it rapidly polymerizes (less than 30 seconds) to cure, resulting in the desired adhesion or seal strength. In 1959, the first cyanoacrylate adhesive Eastman910 (methyl α-cyanoacrylate) was marketed for skin adhesion and hemostasis. Subsequently, a number of cyanoacrylate adhesives were synthesized in various countries, for example, AU-CRYLATE (the main component thereof being n-/iso-butyl α-cyanoacrylate) in USA, HISTOACRYL BLUE (the main component thereof being n-butyl α-cyanoacrylate) in Germany.
The research and production of medical adhesives have been carried out in China since 1962, mainly including FAL (n-butyl/n-octyl α-cyanoacrylate), butyl α-cyanoacrylate, isobutyl α-cyanoacrylate, n-octyl α-cyanoacrylate and the like. These commercialized products have been widely used in clinical applications, but they still have some drawbacks. For example, the resulting polymer has relatively poor flexibility, and the resulting adhesive bond are relatively hard, which are unfavorable for the use in soft organs such as tissue and skin; the degradability is poor due to that single α-cyanoacrylate polymerizes to form a linear polymer, whose linear backbone chain obtained by polymerization of carbon-carbon double bond has a relatively high level of carbon-carbon bond energy, and is difficult to break, so this type of polymer degrades very slowly, and the presence thereof at the wound site for a long time may lead to foreign body reaction, and may cause new inflammation and even impede further wound healing, to thereby reduce the practical value thereof as a surgical adhesive/sealant.
Several patents reported modifications of the ester chain portion, including introduction of more ester linkage sites in the structure, to accelerate the degradation of side chain. U.S. Pat. No. 3,995,641, as filed by Kronenthal et al, discloses a carbalkoxyalkyl cyanoacrylate adhesive, which can form an absorbable polymer in mammalian tissue. Chinese patent CN101180085A discloses a cyanoacrylate structure containing a plurality of ester linkages and spacer groups in its side chain to accelerate degradation.
Although the modifications on side chain in these documents accelerate the degradation of side chain ester, these degradation modes, in fact, all deal with the degradation of the polymer side chain, while the linear carbon-carbon backbone chain of the polymer is still difficult to be degraded and absorbed. Thus, there is still a need to develop a medical adhesive whose polymer backbone chain has better biodegradability and biocompatibility.